Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rheumatoid arthritis is a chronic inflammatory disease that can cause severe pain and disability. Disease management historically was based on a "therapeutic pyramid" in which treatment escalated as symptoms worsened. However, the demonstration of early joint damage in patients with rheumatoid arthritis has emphasized the importance of early identification and treatment. Key features in establishing a diagnosis include joint examinations, assessments of extra-articular manifestations, laboratory tests, and radiologic examinations. Care must be taken to rule out other disorders with symptoms that overlap those of rheumatoid arthritis. Treatment of rheumatoid arthritis typically involves disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and low-dose corticosteroids--often used in combination. A new class of therapeutic agents designed to neutralize inflammatory cytokines has added a new dimension to the therapeutic armamentarium against rheumatoid arthritis. Etanercept, a bioengineered soluble receptor fusion protein that blocks tumor necrosis factor activity, is the first compound in this class to be approved for treatment of patients with refractory rheumatoid arthritis. Therapeutic trials indicate that etanercept can reduce disease activity with relatively few drug-related adverse effects, thus helping persons with rheumatoid arthritis return to more normal, healthy lives.
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PMID:Rheumatoid arthritis and primary care: the case for early diagnosis and treatment. 1040 18

Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been successfully used in patients with rheumatoid arthritis, where it reduces pain and inflammation. Because locally produced proinflammatory cytokines play a role in pain after nerve injury, we investigated whether etanercept can reduce pain and hyperalgesia in an animal model of painful neuropathy, the chronic constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or sham treatment by local near-nerve injection to the injured nerve or by systemic application. Treatment with etanercept reduced thermal hyperalgesia and mechanical allodynia significantly in both modes of application. The effect of etanercept was present in animals that were treated from the time of surgery and in those that were treated from day 6, when hyperalgesia was already present. These results suggest the potential of etanercept as a treatment option for patients with neuropathic pain.
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PMID:Etanercept reduces hyperalgesia in experimental painful neuropathy. 1144 85

A 33-year-old man with generalized vulgar psoriasis type I and psoriatic arthritis was admitted to the Naftalan Special Hospital on February 21, 2000. He was immobile and complained of severe pain in all his joints. Since the patient had suffered from the disease for 10 years without showing any improvement after different therapies, his cutaneous and joint lesions gradually worsened and eventually resulted in generalized psoriasis and mutilating arthritis. Nevertheless, the patient was discharged from our hospital in better condition. To avoid such severe consequences of psoriatic arthritis, we believe that patients with either type I or type II psoriasis should undergo locomotor system screening. It would significantly decrease the number of unrecognized and undiagnosed cases of psoriatic arthritis and allow their early treatment, and prevention of more severe forms. Administration of new therapeutic agents, e.g. Alefacept (IgG1 fusion protein), Etanercept (inhibitor of TNF activity), and Efalizumab (monoclonal antibody that blocks the leukocyte integrin CDIIa/CD18(LFA-1), could provide successful management of the disease in future.
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PMID:Psoriasis vulgaris and arthritis psoriatica gravis mutilans. 1271 92

Etanercept is a dimeric fusion protein based on the p75 tumor necrosis factor (TNF) receptor. It binds to TNFalpha and blocks its biological activity. Subcutaneous etanercept is effective in the treatment of rheumatoid arthritis, psoriatic arthritis, and polyarticular-course juvenile rheumatoid arthritis. More recently, etanercept has shown efficacy in the treatment of adults with ankylosing spondylitis. In randomized, double-blind, placebo-controlled trials, subcutaneous etanercept 25mg twice weekly for 6-24 weeks significantly reduced disease activity in patients with active ankylosing spondylitis. In the largest trial, etanercept produced a response rate of 57% compared with 22% for placebo after 24 weeks (response was determined via the validated ASAS 20 response criteria developed by the Assessments in Ankylosing Spondylitis [ASAS] Working Group). Etanercept therapy significantly improved health-related quality of life in patients with ankylosing spondylitis compared with placebo. The greatest improvements in a 16-week study were seen in the domains of physical functioning, physical role, bodily pain, vitality, and social functioning. Etanercept was generally well tolerated, with few serious adverse events or treatment withdrawals. The most common adverse events were injection-site reactions and minor upper respiratory tract infections.
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PMID:Etanercept: in ankylosing spondylitis. 1516 37

Rheumatoid arthritis is a severe, debilitating condition for which existing therapies are of limited efficacy. In addition, the most common structure of treatment for patients with rheumatoid arthritis has recently been called into question, and many believe it should be reversed so that stronger treatments are administered earlier in the progression of the disease. Pivotal to the changes in rheumatoid arthritis treatment is the introduction of the pro-inflammatory tumor necrosis factor (TNF) antagonists. Overexpression of cytokines in inflamed joints plays an important role in joint inflammation and tissue damage, and the place of cytokines in the pathology of rheumatoid arthritis has offered hope that their antagonism will reduce symptoms and slow the advancement of the condition. With this in mind, etanercept, a fully human soluble TNF receptor fusion protein, was developed. The potency of this novel drug in blocking TNF activity has been shown in animal models and in clinical trials. The latter have demonstrated a positive safety profile and efficacy in reducing pain and the number of tender and swollen joints in rheumatoid arthritis patients. The effects of etanercept have also been observed soon after administration and have been sustained over several years. Etanercept has offered encouragement for those seeking new, more efficacious and less toxic methods of treating rheumatoid arthritis in children, adults and the elderly. In addition to the treatment of adult and juvenile rheumatoid arthritis, etanercept has also demonstrated utility in treating ankylosing spondylitis and psoriatic arthritis.
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PMID:The soluble tumor necrosis factor receptor etanercept: a new strategy for the treatment of autoimmune rheumatic disease. 1519 Mar 85

Rheumatoid arthritis (RA) is a chronic progressive disease of the joints associated with significant morbidity, deformity, and impaired quality of life. A satisfactory remission of disease is seldom achieved, so therapy is aimed at controlling joint damage and pain with preservation of joint mobility. Until recently, NSAIDs, followed by DMARDs, was considered the treatment of choice. However, many patients fail to gain a satisfactory response to DMARDs or response declines over time. Biologics such as IL-1 receptor antagonist (anakinra), and anti TNF-alpha agents (Etanercept, Infliximab, and Adalimumab) are now available. The anti TNF and IL-1 therapies exert their anti-inflammatory action by neutralizing the activities of TNF-alpha and IL-1 respectively. In contrast to older DMARDs, these agents have rapid onset of action with fewer side effects and have pronounced disease reducing activity in patients who have previously been treated with other DMARDs, when administered as monotherapy or in combination with methotrexate. They have been shown to be at least as effective as methotrexate in reducing clinical disease activity and reducing radiographic progression. Biological agents are generally well tolerated, although their long-term safety needs to be determined. Some concerns have been raised that anti TNF-alpha therapy can increase the risk of serious infections, since TNF-alpha plays an important role in host defense. In light of limitations of cost and lack of long-term safety and efficacy data, newer agents for the time being are used as second- or third-line agents in patients with active RA. The dilemma is that which patients with RA are most suitable for such therapy, since it is still not possible to accurately predict which patient with RA will develop severe disease. One alternative approach may be to limit the use in patients who can afford it, and who are at high risk of radiographic progression and disability.
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PMID:Biologics in rheumatoid arthritis. 1563 15

Up to 2 in 1,000 adults in the UK have ankylosing spondylitis. This chronic inflammatory disease causes pain and stiffness in the spine and sacroiliac and peripheral joints, and may also affect the eyes, heart and ungs. Characteristic features include ankylosis of the spine with a progressive loss of spinal mobility. Treatment with NSAIDs and physical therapy can provide symptomatic relief of pain and stiffness, but does not modify the course of the disease (e.g. slow or prevent ankylosis). In general, disease-modifying antirheumatic drugs (DMARDs), such as gold, methotrexate and sulfasalazine, have little or no effect in ankylosing spondylitis. [symbol: see text]Etanercept (Enbrel--Wyeth) and [symbol: see text]infliximab (Remicade--Schering-Plough), two drugs which block the inflammatory effect of tumour necrosis factor (TNF), are now licensed for the treatment of patients with severe ankylosing spondylitis whose symptoms have not responded adequately to conventional therapy. Here we review the place of these TNF antagonists in the management of such individuals.
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PMID:TNF antagonists for ankylosing spondylitis. 1576 84

Etanercept is a commercially available pharmaceutical protein approved for treatment of rheumatoid arthritis, RA. Given subcutaneously, etanercept binds and inactivates soluble tumor necrosis factor-alpha, TNF. Etanercept has a good safety record and is of benefit in lowering pain, inflammation, and joint destruction in RA. RA is mediated by many factors, TNF among them. Malignant myeloma, MM, is a malignant clonal expansion of a post-germinal center B lymphocyte. Since TNF is a necessary growth factor for expansion and maintenance of MM cells, and etanercept binds soluble TNF and is of clinical benefit in RA, etanercept was tried experimentally in MM. Contrary to expectations, etanercept resulted in increased levels of TNF and possibly shortened survival. This paper presents an hypothesis of how this happened. There are two cognate receptors for TNF, termed R1 and R2 and two forms of TNF, soluble and transmembrane. Soluble TNF has greater affinity for TNF-R1 than for TNF-R2. Transmembrane TNF has equal affinity for the two receptors. Since TNF-R2 signaling tends to be more anti-apoptotic and activating of nuclear factor kappa B, NFkB, than is TNF-R1, and TNF-R1 tends to be more pro-apoptotic than is TNF-R2, by inactivating soluble TNF while leaving transmembrane TNF signaling relatively unchanged, etanercept changed the balance in TNF signaling from TNF-R1 towards TNF-R2 weighting. Anti-apoptosis and TNF synthesis would have been up-regulated by that shift. Early data indicates that the common generic antidepressant bupropion may ameliorate Crohn's disease course by down regulating TNF synthesis, maybe it will slow the course of MM as well.
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PMID:Evidence of a mechanism by which etanercept increased TNF-alpha in multiple myeloma: new insights into the biology of TNF-alpha giving new treatment opportunities--the role of bupropion. 1596 26

Therapies directed against tumour necrosis factor (TNF) are effective for the treatment of rheumatoid arthritis and reduce pain scores in this condition. In this study, we sought to explore mechanisms by which TNF contributes to inflammatory pain in an experimental model of arthritis. The effects of an anti-TNF agent, etanercept, on behavioural pain responses arising from rat monoarthritis induced by complete Freund's adjuvant were assessed and compared with expression of TNF receptors (TNFRs) by dorsal root ganglion (DRG) cells at corresponding time points. Etanercept had no effect on evoked pain responses in normal animals but exerted a differential effect on the thermal and mechanical hyperalgesia associated with rat arthritis induced by complete Freund's adjuvant (CFA). Joint inflammation was associated with increased TNFR1 and TNFR2 expression on DRG cells, which was maintained throughout the time course of the model. TNFR1 expression was increased in neuronal cells of the DRG bilaterally after arthritis induction. In contrast, TNFR2 expression occurred exclusively on non-neuronal cells of the macrophage-monocyte lineage, with cell numbers increasing in a TNF-dependent fashion during CFA-induced arthritis. A strong correlation was observed between numbers of macrophages and the development of mechanical hyperalgesia in CFA-induced arthritis. These results highlight the potential for TNF to play a vital role in inflammatory hyperalgesia, both by a direct action on neurons via TNFR1 and by facilitating the accumulation of macrophages in the DRG via a TNFR2-mediated pathway.
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PMID:The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation. 1598 82

A case of juvenile psoriatic arthritis in a 12 year-old boy was reported. The patient had a history of one and half a year of bilateral heel pain, followed by pain in the right knee and ankle and right hip joint. He developed psoriatic lesions affecting his nails and skin. He had increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) contents. Human leukocyte antigen (HLA) B27 was detected but serum rheumatoid factor was not in the patient. A skin biopsy revealed psoriasis and ultrasonography demonstrated synovitis in right knee and ankle. Juvenile psoriatic arthritis was diagnosed based on his physical, laboratory and skin biopsy findings. A treatment with nonsteroidal anti-inflammatory drugs and sulfasalazine produced no effect. Leflunomide in conjunction with anti-TNF biologic agents (Etanercept) was administered, followed by symptomatic improvement 2 weeks later.
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PMID:[Juvenile psoriatic arthritis]. 1770 35


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